In Quest to Eliminate Biofilm, Baker's Yeast Rises to the Challenge

The study of yeast cells may point a way toward eliminating the formation of biofilm on medical devices and implants, according to microbiologists at the Whitehead Institute for Biomedical Research in Cambridge, MA.

Fungal formations caused by Candida albicans envelop devices in a resilient biofilm coating that impairs their functionality. It also engenders infections of the skin, oral cavities, esophagus, gastrointestinal tract, and genitalia. Patients with weakened immune systems are particularly vulnerable to the organism, which causes thousands of deaths each year. Observing that yeast cells stick to the bottoms of plastic laboratory plates, microbiologist Todd Reynolds set out to find a yeast protein responsible for this adherence. "The system that initiates the formation of a biofilm in baker's yeast potentially can hold true for pathogenic Candida, as well," he says. "Once molecules involved in this process are identified, we can search for similar molecules in that fungus," says Reynolds, and ultimately find a way to neutralize them. Reynolds published his research in the February 2 issue of Science in an article coauthored by Whitehead Institute director Gerald Fink.

The researchers have identified yeast genes FLO11 and FLO8. The first encodes a cell-surface glycoprotein required for adhesion to agar, and the second gene expresses a protein that turns on FLO11 expression. Disrupting the FLO11 gene, according to the report authors, stopped the yeast cells from radiating out in their characteristic gauzy floral pattern and prevented the formation of biofilms on hard plastic surfaces. "If there's a comparable gene in Candida and a competitive inhibitor that would interfere with its ability to bind," notes Reynolds, "that could substantially inhibit the fungus from setting up a biofilm or even, perhaps, from adhering to human tissue in an infectious situation."

The fungal biofilm discoveries have been exclusively licensed to Cambridge-based Microbia Inc., a start-up biotech company cofounded by Fink. Although research is still at an early stage--the company tentatively plans to begin animal trials by the end of 2002--Microbia has discussed the technology with device OEMs, who have expressed significant interest. "Ultimately, we would want to partner with several individual device manufacturers by product area," says vice president of legal affairs Sarah Cabot.

Norbert Sparrow